Hot flash: TRPV channels in the brain

Kauer, Julie A.; Gibson, Helen E.

doi:10.1016/j.tins.2008.12.006

Cited by 210 publications

(182 citation statements)

References 93 publications

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“…The TRPV1 receptor is a postsynaptic cation channel that underlies sensation of noxious heat in the periphery, with capsacin (hot chili) as an exogenous ligand. TRPV1 receptors are also expressed in the brain, including the amygdala, periaqueductal grey, hippocampus, and other areas [26,27].…”

Section: The Endocannabinoid Systemmentioning

confidence: 99%

Cannabidiol as a Potential Treatment for Anxiety Disorders

et al. 2015

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Cannabidiol (CBD), a Cannabis sativa constituent, is a pharmacologically broad-spectrum drug that in recent years has drawn increasing interest as a treatment for a range of neuropsychiatric disorders. The purpose of the current review is to determine CBD's potential as a treatment for anxiety-related disorders, by assessing evidence from preclinical, human experimental, clinical, and epidemiological studies. We found that existing preclinical evidence strongly supports CBD as a treatment for generalized anxiety disorder, panic disorder, social anxiety disorder, obsessive-compulsive disorder, and post-traumatic stress disorder when administered acutely; however, few studies have investigated chronic CBD dosing. Likewise, evidence from human studies supports an anxiolytic role of CBD, but is currently limited to acute dosing, also with few studies in clinical populations. Overall, current evidence indicates CBD has considerable potential as a treatment for multiple anxiety disorders, with need for further study of chronic and therapeutic effects in relevant clinical populations.

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Section: The Endocannabinoid Systemmentioning

confidence: 99%

Cannabidiol as a Potential Treatment for Anxiety Disorders

et al. 2015

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“…Since endogenous TRPV1 is expressed in the hippocampus and has been shown to affect Hebbian plasticity through presynaptic mechanisms (Gibson et al, 2008;Kauer and Gibson, 2009), we excluded the possibility that endogenous TRPV1 participated in homeostatic regulation of inhibitory synapses by showing that capsaicin treatment (50 nM) of untransfected neuronal cultures did not affect neuronal firing activity (supplemental Table 2, available at www.jneurosci.org as supplemental material) or inhibitory synaptic transmission (Fig. 4C).…”

Section: Elevated Postsynaptic Spiking Was Sufficient For Increasing mentioning

confidence: 99%

Postsynaptic Spiking Homeostatically Induces Cell-Autonomous Regulation of Inhibitory Inputs via Retrograde Signaling

Peng

Zeng²,

Song³

et al. 2010

J. Neurosci.

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Developing neural circuits face the dual challenge of growing in an activity-induced fashion and maintaining stability through homeostatic mechanisms. Compared to our understanding of homeostatic regulation of excitatory synapses, relatively little is known about the mechanism mediating homeostatic plasticity of inhibitory synapses, especially that following activity elevation. Here, we found that elevating neuronal activity in cultured hippocampal neurons for 4 h significantly increased the frequency and amplitude of mIPSCs, before detectable change at excitatory synapses. Consistently, we observed increases in presynaptic and postsynaptic proteins of GABAergic synapses, including GAD65, vGAT, and GABA A R␣1. By suppressing activity-induced increase of neuronal firing with expression of the inward rectifier potassium channel Kir2.1 in individual neurons, we showed that elevation in postsynaptic spiking activity is required for activity-dependent increase in the frequency and amplitude of mIPSCs. Importantly, directly elevating spiking in individual postsynaptic neurons, by capsaicin activation of overexpressed TRPV1 channels, was sufficient to induce increased mIPSC amplitude and frequency, mimicking the effect of elevated neuronal activity. Downregulating BDNF expression in the postsynaptic neuron or its extracellular scavenging prevented activity-induced increase in mIPSC frequency, consistent with a role of BDNF-dependent retrograde signaling in this process. Finally, elevating activity in vivo by kainate injection increased both mIPSC amplitude and frequency in CA1 pyramidal neurons. Thus, spiking-induced, cell-autonomous upregulation of GABAergic synaptic inputs, through retrograde BDNF signaling, represents an early adaptive response of neural circuits to elevated network activity.

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“…Indeed, there are several indications for this. TRPV1 knockout mice reveal changes in behavior and LTD (Marsch et al, 2007; Gibson et al, 2008;Kauer and Gibson, 2009). In humans, a mutation has been described potentially affecting TRPV1 and/or TRPV3 through a de novo balanced chromosomal translocation (Walter et al, 2004).…”

Section: Journal Of Cell Sciencementioning

confidence: 99%

“…Comparative immunohistochemical analyses of knockout and wild-type animals also confirmed that TRPV1 is present in the brain (Cristino et al, 2006). Endogenous expression of TRPV1 in different parts of the brain, in the spinal cord and in peripheral nociceptive neurons (Steenland et al, 2006;Kauer and Gibson, 2009) have been interpreted as showing involvement of TRPV1 in cognition, pain perception and in neuropsychiatric disorders . Indeed, TRPV1 receptor in the central nervous system is a target for TRPV1-antagonist-mediated analgesia (Cui et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

TRPV1 acts as a synaptic protein and regulates vesicle recycling

Goswami

Rademacher

Smalla

et al. 2010

Journal of Cell Science

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SummaryElectrophysiological studies demonstrate that transient receptor potential vanilloid subtype 1 (TRPV1) is involved in neuronal transmission. Although it is expressed in the peripheral as well as the central nervous system, the questions remain whether TRPV1 is present in synaptic structures and whether it is involved in synaptic processes. In the present study we gathered evidence that TRPV1 can be detected in spines of cortical neurons, that it colocalizes with both pre-and postsynaptic proteins, and that it regulates spine morphology. Moreover, TRPV1 is also present in biochemically prepared synaptosomes endogenously. In F11 cells, a cell line derived from dorsal-root-ganglion neurons, TRPV1 is enriched in the tips of elongated filopodia and also at sites of cell-cell contact. In addition, we also detected TRPV1 in synaptic transport vesicles, and in transport packets within filopodia and neurites. Using FM4-64 dye, we demonstrate that recycling and/or fusion of these vesicles can be rapidly modulated by TRPV1 activation, leading to rapid reorganization of filopodial structure. These data suggest that TRPV1 is involved in processes such as neuronal network formation, synapse modulation and release of synaptic transmitters.Key words: Capsaicin receptor, Synapse, Active zone, FM4-64 dye, Synaptic-vesicle recycling Journal of Cell Sciencefrom rat DRG neurons and mouse neuroblastoma cells, results in increased neuritogenesis and the formation of extensive filopodial structures (Goswami and Hucho, 2007). Surprisingly, most of these filopodia contain elevated levels of TRPV1 at their tips and morphologically resemble elongated club-shaped spines. In the present study we demonstrate that TRPV1 is present in pre-and postsynaptic structures, and that it is transported to synaptic sites by synaptic transport packets. We also provide evidence that TRPV1 regulates filopodial dynamics and vesicle recycling, processes that are important for synaptogenesis. Results TRPV1 localizes to the spines of primary cortical neurons and is present in synaptic protein preparationsOn the basis of our previous work (Goswami and Hucho, 2007), we hypothesized the presence of TRPV1 in synapses. Primary cortical neurons were employed to test this hypothesis. Because the expression level of endogenous TRPV1 in these neurons was too low for immunocytochemical analysis, we expressed TRPV1 for 6 hours in cortical neurons and analyzed its localization. In spite of the short expression period, TRPV1 became enriched in distinct spots resembling synapses (Fig. 1A). To test whether these puncta represent dendritic spines carrying synapses, we co-stained TRPV1 with endogenous pre-and postsynaptic markers. TRPV1 colocalizes with endogenous pre-and postsynaptic marker proteins, including the active-zone protein Bassoon and postsynaptic elements such as GluR2-containing AMPA receptors, NMDA receptors and PSD95 (Fig. 1A,B). We also observed that TRPV1 colocalizes with ProSAP1 (also known as Shank2; a protein that is mainly present in the postsynapti...

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Hot flash: TRPV channels in the brain

Cited by 210 publications

References 93 publications

Cannabidiol as a Potential Treatment for Anxiety Disorders

Cannabidiol as a Potential Treatment for Anxiety Disorders

Postsynaptic Spiking Homeostatically Induces Cell-Autonomous Regulation of Inhibitory Inputs via Retrograde Signaling

TRPV1 acts as a synaptic protein and regulates vesicle recycling

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